1. ¹Department of Pathology and Laboratory Medicine, University of California at Los Angeles School of Medicine, Los Angeles, California
2. ²Department of Pediatrics, University of California at Los Angeles School of Medicine, Los Angeles, California
3. ³Jonsson Comprehensive Cancer Center, University of California at Los Angeles School of Medicine, Los Angeles, California
4. ⁴Department of Microbiology and Immunology, University of California at Los Angeles, Los Angeles, California
5. ⁵Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California
6. ⁶Department of Pathology, Brigham and Woman's Hospital, Harvard Medical School, Boston, Massachusetts
7. ⁷Genetics Department, Medicine Branch, National Cancer Institute, Bethesda, Maryland

Correspondence: Dr. Michael A. Teitell, Department of Pathology and Laboratory Medicine, Center for the Health Sciences, UCLA School of Medicine, 10833 Le Conte Ave., Los Angeles, California 90095-1732. E-mail: mteitell@ucla.edu

Received 22 December 2000.

Abstract

Activation of the TCL1 oncogene has been implicated in T cell leukemias/lymphomas and recently was associated with AIDS diffuse large B cell lymphomas (AIDS-DLBCL). Also, in nonmalignant lymphoid tissues, antibody staining has shown that mantle zone B cells expressed abundant Tcl1 protein, whereas germinal center (GC; centrocytes and centroblasts) B cells showed markedly reduced expression. Here, we analyze isolated B cell subsets from hyperplastic tonsil to determine a more precise pattern of Tcl1 expression with development. We also examine multiple B cell lines and B lymphoma patient samples to determine whether different tumor classes retain or alter the developmental pattern of expression. We show that TCL1 expression is not affected by Epstein-Barr virus (EBV) infection and is high in naïve B cells, reduced in GC B cells, and absent in memory B cells and plasma cells. Human herpesvirus-8 infected primary effusion lymphomas (PEL) and multiple myelomas are uniformly TCL1 negative, whereas all other transformed B cell lines tested express moderate to abundant TCL1. This observation supports the hypothesis that PEL, like myeloma, usually arise from post-GC stages of B cell development. Tcl1 protein is also detected in most naïve/GC-derived B lymphoma patient samples (23 of 27 [85%] positive), whereas most post-GC–derived B lymphomas lack expression (10 of 41 [24%] positive). These data indicate that the pattern of Tcl1 expression is distinct between naïve/GC and post-GC–derived B lymphomas (P < 0.001) and that the developmental pattern of expression is largely retained. However, post-GC–derived AIDS-DLBCL express TCL1 at a frequency equivalent to naïve/GC-derived B lymphomas in immune-competent individuals (7 of 9 [78%] positive), suggesting that TCL1 down-regulation is adversely affected by severe immune system dysfunction. These findings demonstrate that TCL1 expression in B cell lymphoma usually reflects the stage of B cell development from which they derive, except in AIDS-related lymphomas.